Diabetes, Metabolic Syndrome and Obesity (Jun 2020)
Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
Abstract
Feng Yu Kuo, 1, 2 Kai-Chun Cheng, 3 Yingxiao Li, 4 Juei-Tang Cheng, 5 Cheng-Chia Tsai 6, 7 1Cardiovascular Centre, Kaohsiung Veterans General Hospital, Kaohsiung Citty, Taiwan; 2Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 3Pharmacological Department of Herbal Medicine and Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima Unuversity, Kagoshima, Japan; 4Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan; 5Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; 6Department of Surgery, Mackay Memorial Hospital, Taipei City, Taiwan; 7Department of Medicine, Mackay Medical College, New Taipei, TaiwanCorrespondence: Juei-Tang ChengDepartment of Medical Research, Chi-Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan 71004, TaiwanTel +886-6-2517864Email [email protected] TsaiDepartment of Surgery, Mackay Memorial Hospital, No. 92, Sec.2, Chung-Shan North Road, Taipei City 10449, TaiwanTel +886-2-25433535Email [email protected]: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed.Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting.Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs.Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.Keywords: adropin, Enho gene, STAT3, type 1 diabetes, reactive oxygen species
